Preconditioning Human Skin Fibroblasts with 505 nm Blue–Green Light Reduces UVB-Induced Cyclobutane Pyrimidine Dimers

Visible-light preconditioning may complement sunscreen use by enhancing intrinsic DNA damage responses. We pre-irradiated Hs27 human dermal fibroblasts with 505 nm blue–green light (5.0 mW/cm2, 3–10 min; 0.9–3.0 J/cm2) before UVB irradiation (20 mJ/cm2). At 505 nm, the residual cyclobutane pyrimidine dimer (CPD) burden measured 24 h after UVB was reduced when UVB followed immediately or after 3–24 h (with residual CPDs falling to approximately 67% of the UVB-alone level—an approximately 33% reduction—at the most effective 3.0 J/cm2, 24 h condition), whereas protection was lost by 48 h. Under the 0 h interval condition, CPDs were also quantified immediately after UVB to compare the early CPD signal with the 24 h residual endpoint; all three visible wavelengths (505, 470 and 630 nm) lowered the immediate post-UVB signal, but only 505 nm preconditioning sustained the protective effect at the 24 h endpoint. Blue light (470 nm) produced a limited delayed benefit, whereas red light (630 nm) did not confer consistent protection and increased the residual CPD burden under selected conditions. Non-toxic 505 nm exposure primed an amplified NRF2/ARE response to subsequent UVB; XPC and XPD mRNAs rose at 2–6 h, while XPA and XPB declined early. Together, these findings support further evaluation of 505 nm blue–green light as a proof-of-concept, device-oriented strategy for timed photoprotection against UVB-induced photoaging; because these findings were obtained in a single dermal fibroblast model, they will require validation in keratinocytes and more complex skin systems before any practical application.